TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure‐induced stress in mice

• Published in: Cardiovascular therapeutics Vol. 36; no. 5; pp. e12462 - n/a
• Main Authors: Eblimit, Zeena, Thevananther, Sundararajah, Karpen, Saul J., Taegtmeyer, Heinrich, Moore, David D., Adorini, Luciano, Penny, Daniel J., Desai, Moreshwar S.
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.10.2018
• Subjects: Adaptation, Physiological; Animals; Bile; Cardiotonic Agents - pharmacology; Cells, Cultured; cholic acid; Cholic Acids - pharmacology; Cytoprotection; Disease Models, Animal; Exercise Tolerance - drug effects; Heart; Heart Failure - drug therapy; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; INT‐777; Male; Mice, Inbred C57BL; Mice, Knockout; myocardial adaptation; Myocardial Contraction - drug effects; Myocardium - metabolism; Myocardium - pathology; preconditioning; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Signal Transduction - drug effects; TGR5; TGR5; cholic acid; myocardial adaptation; INT-777; preconditioning

Introduction Administration of cholic acid, or its synthetic derivative, 6‐alpha‐ethyl‐23(S)‐methylcholic acid (INT‐777), activates the membrane GPCR, TGR5, influences whole body metabolism, reduces atherosclerosis, and benefits the cardiovascular physiology in mice. Direct effects of TGR5 agonists,...